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Naturally Occurring Polymers—Animals
Published in Charles E. Carraher, Carraher's Polymer Chemistry, 2017
We are beginning to understand some of the language of the genes. We are already aware of the sequences that code for particular amino acids. We are also becoming more aware of the meaning of other sequences. Many of these sequences are involved with transcription regulation. Promoters are DNA sites where the RNA polymerase can bind, leading to the initiation of transcription. They are generally located near the gene. There are a number of these sequences. The CAAT box has a consensus sequence of GGCCAATCT and its presence indicates a strong promoter site. One or more copies of the sequence GGGCGG, called the GC box, are often found upstream of transcription start sites of housekeeping genes. The TATA box has a sequence of TATAAAA.
Epigenetic modifications associated with pathophysiological effects of lead exposure
Published in Journal of Environmental Science and Health, Part C, 2019
Madiha Khalid, Mohammad Abdollahi
Epigenetic mechanisms of Pb-induced neurodegeneration have been investigated in animal studies. Early life exposure of 1.5 mg/kg Pb among infant primates showed increased APP (P < 0.001) expression later at 23 years of age.67,72 The cerebral cortex of 23 years old primates revealed that developmental Pb exposure resulted in a decreased expression of MeCP2 (P < 0.05), Dnmt1 (P < 0.001), and protein level of Dnmt3a (P < 0.001) along with significant increases in the expression of H3K4me2 (P < 0.01) and H3K9ac, H4K8ac, H4K12ac (P < 0.001).72 Pb-induced epigenetic perturbations via remodeling chromatin conformational states, thereby influencing access of specific gene promoters to transcriptional component197 linked with varied neurodegenerative and neuropsychiatric disorders.192 The APP gene promoter is rich in CpG dinucleotides and GC box content, which regulate transcription via DNA methylation and are therefore important for epigenetic reprograming.198 Infantile or early life Pb exposure showed altered expression for 22 genes, and all except two genes were rich in CpG dinucleotides in 5’ untranslated regions (5’UTR). Four up-regulated genes were observed, including neuron-derived orphan receptor 1 (NOR1), Sp1, organic cation transporter 2 (Oct-2), cytosolic phospholipase 2 (cPLA2) and four down-regulated genes including 5-hydroxytryptamine 1B receptor (5HT1B), dynamin 2 (DNM2), dynamin-binding protein (DNMBP) and ras-related protein (RAB-5C).72 Among them, NOR1 is important for neuronal differentiation during brain development and maintenance of neuronal plasticity at a later age,199 Sp1 and Oct-2 are AD-related genes153,200 and cPLA2 is linked to excitotoxicity of neurons and secretory PLA2-IIA (sPLA2-IIA) involving glial cell inflammatory processes.201 Furthermore, Aβ triggers apoptosis in neurons and impairs mitochondrial processes by activating cPLA2 and arachidonic acid.202,203 Pb is also reported to induce anxiety via influencing monoamine and serotonin level in the brain.204,205 Moreover, Aβ in the brain downregulates DNM2 expression.206 DNMBP is linked to late-onset AD207 and RAB-5C has a a role in cell signaling.208